Abstract

Background:

Carbidopa (CD) and levodopa (LD) extended release (CD-LD ER, Rytary^®) capsules are designed to combine both immediate and extended release pharmacokinetics. In the phase 3, randomized, double-blind, ADVANCE-PD trial, patients randomized to CD-LD ER experienced a 1.17-hour greater reduction in OFF time compared to patients randomized to CD-LD IR (p < 0.0001).

Objective:

To compare CD-LD IR optimization to CD-LD ER conversion based on patient dyskinesia status at baseline using data from the ADVANCE-PD trial.

Methods:

This was a retrospective analysis of the ADVANCE-PD study. Patients were categorized by dyskinesia status at baseline into 1) those who had No Dyskinesia (ND), 2) those who had Non-Troublesome Dyskinesia Only (NTDO), and 3) those who had Troublesome Dyskinesia (TD).

Results:

Comparative reductions in OFF time favoring CD-LD ER over CD-LD IR were similar for the ND (–1.08 h, p = 0.0071, n = 183) and NTDO (–1.12 h, p = 0.0104, n = 131) groups, and smaller for the TD group (–0.82 h, p = 0.2382, n = 79). Reductions in OFF time for both CD-LD ER conversion and CD-LD IR adjustment were largest within the ND group and smallest within the TD group (CD-LD ER: ND –2.86 h, NTDO –2.11 h, TD –1.36 h; CD-LD IR: ND –1.78 h, NTDO –0.99 h, TD –0.55 h).

Conclusion:

Responses to both CD-LD IR adjustment and CD-LD ER conversion depended on baseline dyskinesia status. Significant reductions in OFF time with CD-LD ER compared to CD-LD IR were observed in the ND and NTDO groups. In the TD group, comparing CD-LD ER conversion to CD-LD IR optimization, benefits were still observed, but there was less reduction in OFF time, less reduction in troublesome dyskinesia, and fewer patients self-rated themselves much or very much improved than in the ND and NTDO groups. These data suggest that in clinical practice, the best chances for success with conversion from CD-LD IR to CD-LD ER are in patients without TD.

中文翻译：

---

卡比多巴和左旋多巴缓释胶囊在有和没有麻烦和非麻烦的运动障碍患者中。

摘要

背景：

卡比多巴 (CD) 和左旋多巴 (LD) 缓释（CD-LD ER，Rytary ^®）胶囊旨在结合速释和缓释药代动力学。在第 3 阶段、随机、双盲、ADVANCE-PD 试验中，随机分配至 CD-LD ER 的患者与随机分配至 CD-LD IR 的患者相比，OFF 时间减少了 1.17 小时（p  < 0.0001）。

目标：

使用来自 ADVANCE-PD 试验的数据，根据患者基线时的运动障碍状态比较 CD-LD IR 优化与 CD-LD ER 转换。

方法：

这是对 ADVANCE-PD 研究的回顾性分析。根据基线时的运动障碍状态将患者分类为 1) 没有运动障碍 (ND) 的患者，2) 仅有非麻烦性运动障碍 (NTDO) 的患者，以及 3) 有麻烦的运动障碍 (TD) 的患者。

结果：

对于 ND（–1.08 小时，p  = 0.0071，n  = 183）和 NTDO（–1.12 小时，p  = 0.0104，n  = 131）组，有利于 CD-LD ER 和 CD-LD IR 的关闭时间的比较减少相似， TD 组较小（–0.82 小时，p  = 0.2382，n  = 79）。CD-LD ER 转换和 CD-LD IR 调整的关闭时间减少在 ND 组中最大，在 TD 组中最小（CD-LD ER：ND –2.86 h，NTDO –2.11 h，TD –1.36 h； CD-LD IR：ND –1.78 小时，NTDO –0.99 小时，TD –0.55 小时）。

结论：

对 CD-LD IR 调整和 CD-LD ER 转换的反应取决于基线运动障碍状态。在 ND 和 NTDO 组中观察到与 CD-LD IR 相比，CD-LD ER 的关闭时间显着减少。在 TD 组中，将 CD-LD ER 转换与 CD-LD IR 优化进行比较，仍然观察到益处，但关闭时间减少较少，麻烦的运动障碍减少较少，并且很少有患者自我评价自己有很大改善或非常好比在 ND 和 NTDO 组中。这些数据表明，在临床实践中，从 CD-LD IR 转换为 CD-LD ER 的最佳成功机会发生在没有 TD 的患者中。